: Despite increasing knowledge and public awareness about the link between cigarette smoking and adverse health outcomes such as lung cancer and coronary heart disease, nearly 24% of U.S. adults smoke cigarettes, and the smoking prevalence rates in women (22%) and men (26%) have remained relatively constant since 1990. Women's health is of particular concern, since studies show that female smokers may suffer greater health risks than men, and their annual tobacco-related deaths are rapidly approaching those of men. Advances have been made in smoking cessation strategies, but relapse to smoking is still common in people attempting to quit, especially in women who appear to relapse faster and more completely than men, and for whom nicotine patches and gum may be less effective in reducing craving for cigarettes and other withdrawal symptoms. The long-term goal of this research is to decrease smoking prevalence among women through the development of evidence-based smoking cessation strategies - strategies specifically tailored to women's unique physiological responses to nicotine and which address specific barriers to cessation (e.g., withdrawal, negative affect focusing on depressive symptoms, and weight gain), many of which in clinical studies have been shown to have gender-specific influences. The specific aims of this competing renewal are (1) to determine how smoking relapse rates are influenced by the menstrual cycle phase in which smoking cessation is initiated, and (2) to determine the impact of phase during smoking abstinence on potential relapse-related factors: withdrawal and premenstrual symptoms, weight gain, and negative affect, focusing specifically on depressive symptoms. A final, secondary aim will be to identify the cycle phase during which study participants are most likely to relapse following a repeat quit attempt. The proposed 3-year study is a randomized clinical treatment trial [it isn't controlled] of smoking cessation in women (N = 200). Participants enrolled as outpatients will be randomized into two groups for smoking quit dates timed to occur during a particular menstrual cycle phase (follicular or late luteal). Through biochemical testing, participant self-report, and written survey instruments, data will be collected and analyzed over the 26-week treatment period on the following outcomes: smoking status (relapsed/non-relapsed), withdrawal and premenstrual symptomatology, negative affect focusing on depressive symptoms, and the physiological measures of weight, heart rate, and blood pressure. The rationale underlying this research is that once the effects of menstrual cycle phase on these outcomes are understood, the results can be used to inform the development of optimal treatment interventions for women smokers which account for physiologic influences and thereby minimize barriers to starting and maintaining smoking abstinence. Furthermore, this study is expected to provide a framework for future research investigating gender differences in nicotine response, withdrawal, and other cessation-related variables.